Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-β1–induced collagen synthesis

Keloid formation has been linked to aberrant fibroblast activity, exacerbated by growth factors and inflammatory mediators. Prostaglandin E2 (PGE2), synthesized from arachidonic acid by cyclooxygenases (COX) and synthases (PGES), acts as both an inflammatory mediator and fibroblast modulator. Although PGE2 has known antifibrotic effects in the lower airway, its role in dermal fibrosis in general, and keloid formation in particular, remains unclear. This study focused on: (1) the effects of PGE2 on keloid fibroblast migration, contraction, and collagen synthesis and (2) endogenous PGE2 synthesis in response interleukin-1beta. PGE2 decreased keloid fibroblast migration and contraction via an EP2/EP4-cAMP mechanism that disrupted actin cytoskeletal dynamics and reversed transforming growth factor-beta1-induced collagen I and III synthesis. Impaired fibroblast PGE2 production has been linked to lower airway fibrosis and recently to keloid formation. Here, we showed that interleukin-1beta stimulation leads to nuclear factor-kappaB translocation to the nucleus, resulting in up-regulation of COX-2 and microsomal PGE2 synthase 1. Up-regulation of COX-2 in, and secretion of PGE2 by keloid fibroblasts are diminished compared with their normal fibroblast counterparts. We suggest that the antifibrotic effects of PGE2 during keloid formation are potentially diminished due to aberrant paracrine fibroblast signaling. Exogenous PGE2 may supplement decreased endogenous levels and inhibit keloid formation or progression.     

Abnormal movements in Rett syndrome are present before the regression period: a case study.

The suspicion of a diagnosis of Rett syndrome (RTT) is based on clinical criteria that are often not present in the first two stages of the disease, as many of its symptoms will appear at a later age. This sometimes postpones the genetic diagnosis and an early clinical intervention. We present the case of 19-months-old girl who came to the consultation because of an arrest of psychomotor development noticed 5 months earlier without change in sleep pattern, behavior, or social communication. In the observation of 1 hour videotape, she presented subtle stereotypic movements of the face and hands as well as repetitive dystonic posturing of her limbs. A genetic test confirmed the diagnosis of RTT, showing a truncating mutation in the MECP2 gene (R270X). This case confirms that stereotypic movement anomalies, albeit infrequent and subtle, are already present before the regression stage and while maintaining prehension and that, in addition, repetitive dystonic postures may occur. Recognition of these early movement disorders will improve clinicians' ability to perform an earlier diagnosis of RTT.     

Rumination: One Construct, Many Features in Healthy Individuals, Depressed Individuals, and Individuals with Lupus

Rumination has been associated with depression and negative health effects. Yet measures of rumination appear to index multiple constructs that may be differentially related to clinical phenomena. To clarify this literature, we explored convergence and divergence among self-report measures of rumination in 349 undergraduates, 59 depressed adults, 81 healthy adults, and 15 never-depressed adults with Systemic Lupus Erythematosis (SLE). Results suggested there are separate constructs labeled rumination with different relationships to depression. Yet, aggregate measures index a central construct. Depressed individuals ruminated more, across measures, than individuals with SLE, who ruminated more than healthy individuals; this relationship was mediated by dysphoria. Thus, administering multiple rumination measures and attending to constructs assessed by rumination measures appears important in clinical studies.     

Practice standards for optometry and optometric practice accreditation

Background: To assist optometrists to deliver care more efficiently and effectively, in 1995 Optometrists Association Australia decided to develop standards that would assist optometrists in better managing their practices. Existing practice management standards for health professionals were thought to be either not specific enough for optometric practice or to have shortcomings in the context of optometric practice in Australia. Methods: Following a literature search, material previously developed by Optometrists Association Australia to assist practitioners with management of their practices and standards from other professions were used to assist with the development of a draft set of standards for optometric practices in Australia. Successive drafts were circulated for comment to optometrists in practice, non‐optometrists with experience in the development of practice standards for other health professions and to Australian General Practice Accreditation Limited. The comments were used to refine the standards and the accreditation guidelines to their final form. Results: Optometric Practice Standards suitable for use in a practice accreditation program were developed. The standards comprise seven sections—Practice administration, Quality assurance, Rights and needs of the patient, Practice services, Practice facilities, Communication and Patient records. These sections are divided into criteria that provide the detail of the requirements of the standard. Indicators describing how criteria can be assessed accompany the criteria.     

Perceived adherence to prescribed treatment in juvenile idiopathic arthritis over a one‐year period

Objective

To document perceived adherence to treatment (taking medications and performing exercises) in patients with juvenile idiopathic arthritis (JIA) over a 1‐year period and to identify related factors.

Methods

We surveyed parents of patients with JIA at the Montreal Children's Hospital and British Columbia's Children's Hospital in Vancouver. Parents were asked to respond to a series of questionnaires every 3 months over a 12‐month period. Perceived adherence was evaluated on a 100‐mm visual analog scale (VAS) in the Parent Adherence Report Questionnaire (PARQ). Parental coping, distress, child function, disease severity and duration, perceived helpfulness of treatment, problems encountered, and sociodemographic data were also assessed.

Results

The mean age of our sample of 175 children was 10.2 years; mean age at diagnosis was 6.1 years and mean disease duration was 4.1 years. Perceived adherence to medications was consistently high, with average adherence at baseline, 3, 6, 9, and 12 months being 86.1, 91.7, 90.4, 92.0, and 88.8, respectively, on the PARQ VAS. Perceived adherence to exercise was lower but remained steady, with corresponding means of 54.5, 64.1, 61.2, 63.0, and 54.3, respectively. Using generalized estimating equation analysis, factors associated with higher perceived adherence to medications included perceived helpfulness of medications and lower disease severity; those associated with higher perceived adherence to exercise were younger age of the child, child involvement in responsibility for treatment, and higher perceived helpfulness of the treatment.

Conclusion

Belief in helpfulness of treatment is associated with higher parental perceived adherence to treatment.     

An approach to protein restriction in children with renal insufficiency

Children with mild to moderate renal insufficiency may be at an increased risk for developing glomerulosclerosis and subsequent renal failure. Low protein diets (LPD) have been shown to delay the progression of renal insufficiency in laboratory animals and may be of benefit in adult humans. The nutritional costs of a LPD in adults are reportedly minimal. We review the protein and caloric requirements of growing children and discuss the potential harmful effects and benefits of an LPD in this population. We also discuss dietary adherence and the difficulty of designing an LPD for children. We conclude that the protein content of a typical American diet can safely be reduced to, but not below, the recommended daily allowance for protein if diets are carefully planned, patients and their parents extensively counseled, and if dietary supplements are given to help meet the caloric and vitamin-mineral nutrient needs of growing children. In addition, ongoing nutritional assessment, counseling, and frequent monitoring of growth, diet and biochemical indicators of protein status are essential for maintaining the health of these children.     

Development of the Home Care Client Satisfaction Instrument

Abstract Client (patient) satisfaction has been studied extensively in the health care sector, yet those receiving home health care services have been the focus of few studies. The purpose of this study was to test the reliability and validity of the Home Care Client Satisfaction Instrument (HCCSI). A total of 400 clients, randomly selected from 20 randomly chosen home care agencies in one state, completed the HCCSI and demographic form. Most respondents were older adults with multiple health problems and their families or informal support systems. Since data were skewed, item analysis was used. The revised instrument (HCCSI-R) is unidimensional and includes 12 items rated on a 5-point Likert scale measuring specific aspects of care. In addition, there are three global measures of satisfaction rated on a 10-point scale. All items except one had significant item-total correlations greater than .59. The total score correlates with likeliness to recommend the agency to others (.37, p = .0001), showing some evidence for criterion-related validity.     

Effect of Food on the Pharmacokinetics of a New Hydroxypropyl-β-Cyclodextrin Formulation of Itraconazole

Study Objective . To compare the pharmacokinetics of a single 100-mg oral dose of itraconazole administered as 10 ml of a 10-mg/ml itraconazole solution in hydroxypropyl-β-cyclodextrin under fasting versus postprandial conditions. Design . Open-label, two-way, randomized, crossover study. Setting . Janssen Research Foundation, Belgium. Patients . Twelve healthy volunteers. Interventions . Blood samples were obtained for pharmacokinetic analyses immediately before dosing and at regular intervals up to 96 hours after each dose. Blood and urine samples were obtained for hematologic, biochemical, and urinary safety analyses at baseline and at the end of the study. Measurements and Main Results . The mean peak plasma concentrations of both itraconazole and its active metabolite hydroxy-itraconazole were significantly higher under fasting conditions than under postprandial conditions. The mean times to peak concentration for both the parent compound and its metabolite were significantly shorter under fasting than under nonfasting conditions. The mean areas under the curve (AUC_0–∞ and AUC_{0–24 hrs}) were also significantly higher under fasting than under postprandial conditions. Conclusions . Our findings suggest that the higher bioavailability of this new formulation of itraconazole may be of benefit in seriously ill patients who are not able to ingest adequate quantities of food. The fact that the solution was also well tolerated and was not associated with clinically significant changes in any laboratory value further underscores the potential utility of this dosing form.